Cognitive Profile of Zonisamide and Valproic Acid in the Treatment of Idiopathic Generalized Epilepsy: A Comparative Observational Study

INTRODUCTION: Calls for an alternative to valproic acid (VPA) as drug of choice for idiopathic generalized epilepsies (IGEs) have intensified since the recent International League Against Epilepsy recommendation that the drug should not be administered to women of childbearing age. Zonisamide (ZNS), a third-generation antiepileptic drug, has proven effective in generalized seizures and could be considered an alternative to VPA in this population. OBJECTIVES: The present study was designed to examine possible differences in cognitive profile between ZNS and VPA as monotherapy in patients with IGE in real-life settings. METHODS: We conducted a comparative, descriptive, observational, retrospective cohort study in two groups of patients diagnosed with IGE treated with ZNS ≥200 mg/day or VPA ≥1000 mg/day as stable monotherapy for at least the previous 6 months. We used specific neuropsychological tests for short- and long-term mnemonic functions, working memory, visuospatial speed, attention and processing speed, verbal fluency, executive functions, visual perception, abstraction, anxiety, depression, and apathy. RESULTS: We included 16 patients in the study: eight in the VPA and eight in the ZNS group. Significantly superior mean scores were obtained by the VPA group in working memory (Forward Digits test) and by the ZNS group in execution time for the Rey–Osterrieth complex figure test. No statistically significant differences were found between the groups in the remaining tests. CONCLUSION: Zonisamide as monotherapy has a similar cognitive profile to that of VPA in patients with IGE. The final treatment selection setting should be individualized. ZNS may be a reasonable alternative to VPA in some cases in this population.